Synthetic biology: Stanford, UC Berkeley engineering a new frontier

Most people look at the cedar in Drew Endy's front yard and admire its graceful green boughs, heavy with needles, sap and cones.

Endy sees something much different: an industrial manufacturing platform, waiting to be exploited.

"I dream we could someday reprogram trees that could self-assemble a computer chip in your front yard," exudes the brilliant and intense Stanford University bioengineer, who has emerged as a leading evangelist in the new field of synthetic biology.

One gene at a time, Endy and other elite teams of Bay Area scientists are striving to design and build organisms unlike anything made by Mother Nature.

It's not yet possible to create artificial life from scratch. But it's getting closer, through projects that essentially swap out a cell's original operating system for a lab-designed one. These made-to-order creations then can be put to work.

The Human Genome Project gave us the ability to read nature's instruction manual -- DNA -- like words in a book. But the real opportunities, scientists say, lie in our ability to not only read genetic code, but to write it, then build it using off-the-shelf chemical ingredients, strung together like holiday lights. It is the creation of new genomes -- and a new frontier in bioengineering.

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Synthetic biology works because biological creatures are, in essence, programmable manufacturing systems. The DNA instruction manual buried inside every cell -- its software, in a sense -- can be replaced with a man-made version, giving us the ability to tell it what to make.

This presages the distant day when Endy's big Menlo Park cedar churns out computer chips, not cones. Or makes cancer-fighting drugs. Or fuels. Or building materials. Or anything else.

There are concerns about safety and ethics. In the wrong hands, lone villains or rogue regimes could unleash dangerous life forms. A review in 2010 by a White House commission concluded the field needs monitoring, but the risks are still limited.

Synthetic biology is different from genetic engineering, which simply inserts a gene from one organism into another.

"Syn biologists" are engineers who construct whole new genomes -- using made-to-order parts from foundries, or "fabs," much as industry orders up cast and machined metal parts. UC-Berkeley researcher Chris Anderson is building tumor-killing bacteria. In Emeryville, Amyris Biotechnologies adds genes to yeast or bacteria to make novel biofuels. The company LS9 of San Carlos is engineering bacteria that can make hydrocarbons for gasoline, diesel and jet fuel.

Ton Subsoontorn and Jerome Bonnet are post-doc grad students working on a DNA project called "Totally RAD" in their lab at Stanford University on May 10, 2012. (Norbert Von Der Groeben)

They might use naturally existing genes, but they apply them for a new purpose. They might redesign them. Or they might design genes from scratch, like Legos.

Frustrated by the lengthy, ad hoc and trial-and-error progress of current "bio-manufacturing" techniques, the National Science Foundation (NSF) and the Pentagon are funding foundries to produce the stuff of life.

A $1.4 million NSF grant established the Emeryville-based BIOFAB lab, led by UC Berkeley and Stanford engineers. It is expected to produce thousands of free standardized DNA parts -- and the publicly available codes needed to assemble them.

These BIOFAB parts are essential to the ambitions of the Synthetic Biology Engineering Research Center, or SynBERC, a prominent coalition of biology research labs supported by $23 million of NSF funding. Its goal is to make biology easier engineer. It includes University of California campuses at Santa Cruz, Berkeley and San Francisco, as well as private biotech companies and venture capital firms.

The Pentagon's science wing, the Defense Advanced Research Projects Agency, has awarded a coveted $3.2 million grant to Stanford and $8 million to Emeryville-based company Amyris, co-founded by UC Berkeley's Jay Keasling.

The DARPA program, known as Living Foundries, "is focused on developing currently unattainable technologies and products ... including fluoropolymers, antifungal agents, enzymes, lubricants and coatings, as well as biosensors," DARPA program director Alicia Jackson wrote in an email.

The commercial market has jumped in, as well, selling genes or stitched-together gene sequences. The components can be ordered from companies such as Agilent in Santa Clara or DNA2.0 in Menlo Park. All they need is a credit card.

It's not easy to jump-start life. Almost any scientist can type out gene sequences on a computer, order the genes and then assemble them.

But getting them to communicate to do what you want them to do? That's far tougher.

Keasling has succeeded, making the first bona fide product using synthetic biology: a lifesaving anti-malarial medicine, artemisinin.

His team dismantled three organisms, extracted the genes they wanted, and then custom-built a new genome. But this wasn't just any genome: It held the instructions needed to produce chemicals for artemisinin.

Routine production of the drug is under way, with a goal of manufacturing 35 tons this year.

"It's like brewing beer or wine -- but instead of alcohol, you have your chemical of choice come out. And it is completely renewable," said Keasling, a UC-Berkeley professor of chemical engineering who is also founding head of the Synthetic Biology Department at Lawrence Berkeley National Laboratory.

What worked for artemisinin can work for other products, Keasling said.

"There's no reason why you can't produce petroleum from microbes," he said. "Or plants to clean up the environment, sucking carbon out of the atmosphere."

Others are moving toward the ultimate step: creating life in the laboratory.

Genome-sequencing maverick J. Craig Venter leaped forward in 2010, when his team in Baltimore created the first self-replicating "synthetic" bacterial cell -- proving that genomes can be designed on computers, made in a lab, transplanted into a cell and "booted up" to replicate itself.

As proof, Petri dishes full of its progeny thrive in Venter's lab.

Endy is reminded of the field's potential every time he pedals his bicycle out a driveway blanketed by his cedar's pollen.

"Holy cow," he said. "Imagine this surplus capacity! Biology is the most incredible manufacturing platform on the planet."